Stable organic calcium salt solutions adapted for injection



Patented l l ov. 19; 1940 UNITED STATES PATENT OFFICE s'mnm ORGANIC cALcmM SALT sownous ADAPTED ron INJECTION Ernst Sturm and Richard Fleischmann, Berlin, Germany, assignors to the firm of Johann A. Wiilfing, Chemische Fabrik, Berlin, Germany, a German company No Drawing. Application November I, 1938; S

rial No. 239,408. In Germany April 27, 1938 '8 Claims; .(01. icy-ca) This invention relates to the production of formation of the stabiliser for example with calstable solutions of calcium sodium lactate and cium oxide or sodium carbonate or with bothsolutions adapted for injection. substances. 1

Solutions of calcium'sodium lactate are only In the use of an alkaline earth glucona-te and 5 stable and thus also utilisable per se forinjecan alkali gluconate as stabiliser, an addition 5 tion purposes when the content 'in calcium socompound of these two substances can be added dium lactate does not exceed 5%. Solutions with to the calcium sodium lactate solution. Natua higher content are not stable, that is, after a rally it is also possible to make the desired stable more or less extended period, there takes place solution by the solid initial substances being disa flaky separation and a crystallisation so that solved together or by calcium sodium lactate be: 10 's ich solutions are unsuitable for injection puring dissolved in a solution of, for example calpcses. The solutions having up to 5% "calcium cium-gluconate.

sodium lactate are,'on the other hand, not suit- As already stated above, stable solutions with able on account of their deficient content in a sufliciently high calcium content are attained calcium, in this way, the further advantage being at- 15 Thus, calcium sodium lactatesolutions could "tained that on the addition of calcium gluconate not be used for parenteral calcium therapy althe content in calcium of the solutions is raised. though calcium sodium lactate is, per se, par- By the use of these solutions, no phenomena of ticularly suitable, since the phenomena of ininflammation or pains were given in the case of 20, fiammation and pains do not occur with intraintramuscular injection and the heating feeling muscular injection, and 'in the case of intra; did not occur with intravenous-injection which venous injection the unpleasant heating feeling, g accompanies the injection of other calcium salts. which otherwise occurs with calcium salts. Example I It has now been found that stable calcium sodium lactate solutions containing a higher perof C u Sodium c e, d 25 centage of calcium sodium lactate and adapted s. of calcium gluconate are dissolved in about for injection can be made by t addition t 60 ccs. of boiled distilled water, with heating. the solution as stabilising agent of an alkaiine The Solution 18 e p to 100 Wlth boiled earth gluconate and preferably i it distilled water and again sterilised. This soluthereto also an alkali gluconate, 1 tion is sufiiciently stable, whereas from a solu- 30 Calcium gluconate is particularly it m if tion of 6.5 gins. of calcium sodium lactate in 100 necessary together ith sodium 'gluconate, cos. of water without the addition of gluc'onate,

Strontium gluconate also gives good results. filled into 9411111011168, Crystals Separated Out after Particularly highly concentrated stable solu- 3 dayss5 tions can be attained iii-with an addition or an Example H alkaline earth gluconate and an alkali gluconate 7.5 gins. of calcium sodium lactate are dissolved the solutlon made slightly acid, is in about 60 cos. of hot boiled distilled-water.

P PH Value h Weakly There are added to the solution with heating, 4.5

acld, reactlon can be attamed by means 0; gms. of calcium gluconate and a solution of 40 Come q 4.06 gms. of gluconic acid in about 20 cos. of

In tms way.stable (calcium lactate solutmns water, which has been neutralised with 1.1 gms.

t made wlth' example of catcmm of sodium carbonate. The solution is now made (hum lactate are Particularly liable I up to 100 ccs.'with boiled water and filled as in for parenteral injection. The calcium content Example I gemkfie mm ampoules and again of these solutions is sufiiciently high and owingsterilised is sumcienfly smug w 5 to the added Stabmsmgagent flaking or A solution of '7 .5 gins. of calcium sodium lac tallisation of the calcium sodium lactate is tate in 100 cos. of distilled-water filled into amavolded so that Stable and consequnfly utms poules becomes on the contrary, flocculent after able solutions are obtained.

50. The stabilising agent can be added as Such to Zgtday; andshas almost entirely crystallised out 60 the calcium sodium lactate solution or it can be ay E I In produced by conversion in the calcium sodium :mmpe 1 lactate solution, e. g., by gluconic acid being 8.4 gmsl of calcium sodium lactate are disadded to the calcium sodium lactate solution and solved with heating in about 60 ccs... of boiled this gluconic acid being then converted for the distilled water and 3.65 gms. of calcium gluconate and 3.2 gms.'of gluconic acid are. added to the solution. Theacid solution is now adjusted with sodium carbonate to a pH value of 6.2 to 6.6 and is made up with boiled distilled water to 100 ccs. After germ-free filtration, filling into am-'- poules andsterilisation, this solution will keep for along time.

On the contrary, crystals separate out after seven days from a calcium sodium lactate solution of 8.4% filled into ampoules.

Example IV' gms. of calcium sodium lactate are dissolved .with boiling with 54 gms. of calcium gluconate in 750 ccs. of water. A second solution with neutral reaction is prepared from 49 gms. of gluconic acid (lactone), 13.25 gms. of sodium carbonate and 200 ccs. of water; the sodium carbonate. being gradually added to the boiling gluconic acid solution. After both solutions have been filtered, they are mixed together. and boiled with reflux cooling for 1 hour. After cooling,

the solution is made up with boiled distilledwater to 1000 ccs., acidified with lactic acid to a pH value of 6.6, and, after germ-Tree filtration,

sterilised.

2 Example V 6.5 gms. of calcium sodium lactate are dissolved in 60 ccs. of water with boiling. During the boiling, 2.75 gms. of anhydrous strontium gluconate isslowly added. A second solution is prepared from 2.4gms. of gluconic acid. which is dissolved in 30 ccs. of water and neutralised with 0.65 gms.

tion containing in excess of 5' percent of calcium sodium lactate, and also containing at least 3.65

percent of calcium gluconate.

3. A' stable organic calcium salt solution suitable for injection, comprising an aqueous solution containing in excess of 5 percent of calcium sodium lactate, and also containing a stabilizer comprising calcium gluconate in a proportion of at least 3.65 percent and an alkaline gluconate.

' r 4. A stable organic calcium salt solution suitable for injection, comprising an aqueous solution containing in excess of 5 percent of calcium sodium lactate, and also containing a stabilizer comprising calcium gluconate in a proportion of at least 3.65 percent and sodium gluconate.

5. A stable organic calcium salt solution suitable for injection, comprising an aqueous solution containing per hundred ccs of solution from 6.5 to 8.4 grams of calcium sodium lactate, 3.65 to 6.4 grams of calcium gluconate, and also containing sodium gluconate and gluconate acid and having a pH value between 6.2 and 6.6, said gluconates and gluconic acid being effective as a stabilizer.

6. A stable organic calcium salt solution suitable for injection, comprising an aqueous solution containing in excess of 5 percent of calcium sodium lactate; andalso containing a stabilizer comprising at least one alkaline earth gluconate, an alkali gluconate, and an organic acid selected from the group consisting of gluconic and lactic acids and having a pH value between 6.2 and 6.6.

7. A stable organic calcium salt solutionsuitcontaining in excess of 6.5 percent of calcium sodium lactate, and also containing a stabilizer comprising calcium gluconate in a. proportion of at least 3.65 percent and an alkaline gluconate .and having a pH value between 6.2 and 6.6.

8. A stable organic calcium salt solution suitable for injection, comprising an aqueoussolution containing in excess of 6.5 percent of calcium sodium lactate, and also containing a stabilizer comprising calcium gluconate in a proportion of V at least 3.65 percentv and sodium gluconate and having a pH value between 6.2 and- 6.6.

ERNST s'roRM. RICHARD FLEISCHMANN. 

